Cancer stem cell (CSC) inhibitors: a review of recent patents (2012-2015)

ABSTRACT

Introduction: Cancer stem cells (CSCs) mediate tumor initiation and maintenance. These cells are chemoresistant and possess characteristics such as self-renewal, pluripotency, plasticity and differentiation. They have aberrant or altered signaling pathways depending on tumor microenvironment, tumor type, etc. CSCs are responsible for highly aggressive and invasive form of the disease following chemo- and/or radiotherapy. Eliminating CSCs is likely to improve the survival rate in patients. Several anti-CSC strategies and associated targets have been proposed and validated till date.

Areas covered: The main emphasis is on the patent applications/patents filed/granted in the last few years (2012–2015). The anti-CSC agents are discussed under two broad headings – small- and macromolecules. Different subclasses are further elaborated, e.g., kinase inhibitors, polypeptides, etc.

Expert opinion: Clinical development of small- and macromolecular anti-CSC therapeutics is underway. Few of these agents act on validated targets such as kinases. Potential problems with these agents can be envisaged based on our understanding of target biology. Other issues governing the choice of small- versus macromolecules include druggability of the target, ease of its modulation and the presence of compensatory mechanisms. Drug repurposing can be attempted to discover newer anti-CSC drugs quickly.

KEYWORDS:

• CSC
• STAT3
• notch
• hedgehog
• Wnt/β-catenin
• sumoylation
• γ-secretase
• lignan lactones
• IL-1R1

Article highlights

• Targeting of CSCs is an attractive approach to curb the aggressive, refractory and chemoresistant cancerous states

• CSC markers have been identified in several cancerous tissues

• A variety of CSC pathway inhibitors (small- and macromolecules) have been identified

• Kinases represent a major target class for developing anti-CSC therapeutics

• Newer strategies for killing CSCs are emerging and getting validated

• The present review attempts to outline these major strategies of CSC elimination

This box summarizes key points contained in the article.

Declaration of interest

PS Kharkar is an External Consultant to Godavari Biorefineries Ltd, Mumbai, India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was funded by BIRAC, Department of Biotechnology, Government of India, India grant number BT/BIPP0887/33/14.